Placebo in history

Placebo in history is the account of the changing understanding of the phenomena of the placebo effect and term "placebo".

The word was first used in a medicinal context in the late 18th century to describe a "commonplace method or medicine" and in 1811 it was defined as "any medicine adapted more to please than to benefit the patient". Although this definition contained a derogatory implication[1] it did not necessarily imply that the remedy had no effect.[2]

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The word placebo itself originated from the Latin phrase for I shall please.[3] It is in Latin text in the Bible (Psalm 114:9, Vulgate version by Jerome (116 in many modern editions), "Placebo Domino in regione vivorum", "I shall please the Lord in the land of the living"). Jerome translated as "I shall please" (placebo), the Hebrew word "ethalech", "I shall walk with" as in "I shall be in step with".

In Chaucer's Canterbury Tales, Placebo is the name of the sycophantic brother of January in "The Merchant's tale".

This word gave its name, placebo, to the Office of the Dead church service. From that, a singer of placebo became associated with someone who falsely claimed a connection to the deceased to get a share of the funeral meal, and hence a flatterer, and so a deceptive act to please.[1]

Doctors and surgeons such as Ambroise Paré traditionally emphasized the importance of consoling the patient through the use of 'placebos'. This is the title page to one of Paré's works.

In the practice of medicine it had been long understood that, as Ambroise Paré (1510–1590) had expressed it, the physician's duty was to "cure occasionally, relieve often, console always" ("Guérir quelquefois, soulager souvent, consoler toujours"). Accordingly, placebos were widespread in medicine until the 20th century, and were often endorsed as necessary deceptions.[4]

According to Nicholas Jewson, eighteenth century English medicine was gradually moving away from a model in which the patient had considerable interaction with the physician – and, through this consultative relationship, had an equal influence on the physician's therapeutic approach. It was moving towards a paradigm in which the patient became the recipient of a more standardized form of intervention that was determined by the prevailing opinions of the medical profession of the day.[5]

Jewson characterized this as parallel to the changes that were taking place in the manner in which medical knowledge was being produced; namely, a transition from "bedside medicine", through to "hospital medicine", and finally to "laboratory medicine".[6]

The last vestiges of the "consoling" approach to treatment were the prescription of morale-boosting and pleasing remedies, such as the "sugar pill", electuary or pharmaceutical syrup; all of which had no known pharmacodynamic action, even at the time. Those doctors who provided their patients with these sorts of morale-boosting therapies (which, while having no pharmacologically active ingredients, provided reassurance and comfort) did so either to reassure their patients while the Vis medicatrix naturae (i.e., "the healing power of nature") performed its normalizing task of restoring them to health, or to gratify their patients' need for an active treatment.

In 1811, Hooper'sQuincy's Lexicon–Medicum defined placebo as "an epithet given to any medicine adapted more to please than benefit the patient". In 1903 Richard Cabot said that he was brought up to use placebos,[4] but he ultimately concluded by saying that "I have not yet found any case in which a lie does not do more harm than good."[7]

Metallic Tractors. Caricature of a quack treating a patient with Perkins Patent Tractors by James Gillray, 1801.

The first to recognize and demonstrate the placebo effect was English physician John Haygarth in 1799.[8] He tested a popular medical treatment of his time, called "Perkins tractors", which were metal pointers supposedly able to 'draw out' disease. They were sold at the extremely high price of five guineas, and Haygarth set out to show that the high cost was unnecessary. He did this by comparing the results from dummy wooden tractors with a set of allegedly "active" metal tractors, and published his findings in a book On the Imagination as a Cause & as a Cure of Disorders of the Body.[9]

The wooden pointers were just as useful as the expensive metal ones, showing "to a degree which has never been suspected, what powerful influence upon diseases is produced by mere imagination".[10] While the word placebo had been used since 1772, this is the first real demonstration of the placebo effect.

John Haygarth was the first to demonstrate the placebo effect in 1799.

In modern times the first to define and discuss the "placebo effect" was T.C Graves, in a published paper in The Lancet in 1920.[11] He spoke of "the placebo effects of drugs" being manifested in those cases where "a real psychotherapeutic effect appears to have been produced".[12]

At the Royal London Hospital in 1933, William Evans and Clifford Hoyle experimented with 90 subjects and published studies which compared the outcomes from the administration of an active drug and a dummy simulator ("placebo") in the same trial. The experiment displayed no significant difference between drug treatment and placebo treatment, leading the researchers to conclude that the drug exerted no specific effects in relation to the conditions being treated. [13] A similar experiment was carried out by Harry Gold, Nathaniel Kwit and Harold Otto in 1937, with the use of 700 subjects.[14]

In 1946, the Yalebiostatistician and physiologistE. Morton Jellinek described the "placebo reaction" or "response". He probably used the terms "placebo response" and "placebo reaction" as interchangeable.[15]Henry K. Beecher's 1955 paper The Powerful Placebo was the first to use the term "placebo effect", which he contrasts with drug effects. [16] In 1961, Beecher found[17] that patients of 'enthusiastic' surgeons experienced greater levels of chest pain relief than those receiving treatment from skeptic surgeons.[7]

In 1961 Walter Kennedy introduced the word nocebo to refer to a neutral substance that creates harmful effects in a patient who takes it.[4][18]

The word obecalp, "placebo" spelled backwards, was coined by an Australian doctor in 1998 when he recognised the need for a freely available placebo.[19] The word is sometimes used to make the use or prescription of fake medicine less obvious to the patient.[20]

It has been suggested that a distinction exists between the placebo effect (which applies to a group) and the placebo response (which is individual).[21]

Some statements about the role of placebos in doctor patient relationship are:

Cooper (1823, p. 259): "[When applying] the compound decoction of the sarsaparilla ... [in cases of] irritable ulcer, ... some think it placebo; others have a very high opinion of its efficacy ... [when it is used] after the use of mercury, it diminishes the irritability of the constitution, and soon soothes the system into peace".

Shapiro[1] (p. 656): "[This use of the term "placebo" is a form of] positioning.... Introduction of the word placebo to describe a class of treatments not previously specified was an important development in the history of methodology and medicine."

Handfield-Jones (1953): "some patients are so unintelligent, neurotic, or inadequate as to be incurable, and life is made easier for them by placebo".

Platt (1947, p. 307): "the frequency with which placebos are used varies inversely with the combined intelligence [sic] of the doctor and his patient".

Steele (1891, pp. 277–8): "To argue with a man, and especially with a woman, that there is little the matter with them might be thought injudicious, and to advise them to return at a more convenient occasion requires more time and resolution than writing out a prescription or administering a placebo."

But Shapiro[1] (p. 679): "If a placebo is prescribed by a physician because it is thought that it will help the patient, then it is a specific [remedy] and therefore not a placebo [at all]."

An editorial in the British Medical Journal of 19 January 1952 (p. 150): "But it is a fallacy to suppose that an inactive medicine can do no harm. If prescribed in a perfunctory way for a patient needing explanation and reassurance it may increase faith in his disease rather than in the remedy, and a doctor who gives a placebo in the wrong spirit may harm the patient."

Pepper (1945, p. 411): "There may be a time when during the carrying out of diagnostic tests it is undesirable to give potent medicine lest it interfere with the tests and yet the patient must be encouraged by treatment.... There is a certain amount of skill in the choice and administration of a placebo. In the first place, it must be nothing more than what the name implies a medicine without any pharmacologic action whatever. Even a mild sedative is not a true placebo. Secondly, its name must be unknown to even the most inveterate patient who knows most drugs by name and is always quick to read the prescription. If the medicines named are familiar, the type of patient who needs a placebo will promptly exclaim that this or that drug had been tried and 'had not helped me' or 'had upset my stomach'. It is well if the drug have a Latin and polysyllabic name; it is wise if it be prescribed with some assurance and emphasis for psychotherapeutic effect. The older physicians each had his favorite placeboic prescriptions – one chose Tincture of Condurango, another the Fluidextract [sic] of Cimicifuga nigra. Certainly this latter by its Latin name might be expected to have more supratentorial action than if one merely wrote for the Black Cohosh, and Condurango would be more effectual than sugar of milk." Pepper's assertion that a placebo "must be nothing more than what the name implies" – namely that it must be "a medicine without any pharmacologic action whatever" – in order for it to be called a placebo, is most significant.

Findley (1953, pp. 1824, 1826): "[If the placebo is not] used as an instrument of deception, but as a technique for cementing the emotional bond which must attach doctor to patient if any form of treatment is to be really successful ... [it was] the most important weapon the physician has ... [specifically because] in proportion as this [doctor-patient] bond is firm, the [patient's] need for drugs will likely diminish."

Leslie (1954, p. 854): "Because medicine has been so concerned with its scientific growth, too little attention has been paid to advancing the art of medicine, to which therapy with placebos belongs, and consequently knowledge of the use of placebos has not progressed significantly."

Carruthers, Hoffman, Melmon & Nierenberg (2000, p. 1268): "In clinical practice, where a majority of patient visits are for conditions that cannot be explained on a pathophysiologic basis of for which no specific treatment is available, it is essential that physicians understand the concepts and principles of placebos and placebo effects and, when appropriate, use them correctly."

Cochrane[22] "It is important to distinguish the very respectable, conscious use of placebos. The effect of placebos has been shown by randomised controlled trials to be very large. Their use in the correct place is to be encouraged. What is inefficient is the use of relatively expensive drugs as placebos."